Amphiphilic siloxane-containing (meth)acrylamides and uses thereof

ABSTRACT

The invention provides an amphiphilic siloxane-containing (meth)acrylamide which comprises one sole (meth)acrylamido group, one sole tris(trimethylsiloxy)silyl group, and one polyethylene glycol segment which is either dangling polymer chain or a hydrophilic linker between the (meth)acrylamido group and the tris(trimethylsiloxy)silyl group. The present invention is also related to a polymer, an actinically-crosslinkable silicone-containing prepolymer, a silicone hydrogel polymeric material, or a silicone hydrogel contact lens, which comprises monomeric units derived from an amphiphilic siloxane-containing (meth)acrylamido group, one tris(trimethylsiloxy)silyl group of the invention. In addition, the invention provides a method for making silicone hydrogel contact lenses using a water-based lens-forming formulation comprising an amphiphilic siloxane-containing (meth)acrylamido group, one tris(trimethylsiloxy)silyl group of the invention and/or an actinically-crosslinkable silicone-containing prepolymer of the invention.

This application claims the benefits under 35 USC §119 (e) of U.S.provisional application No. 61/737,181 filed Dec. 14, 2012, incorporatedby reference in its entirety.

The present invention is related to a class of amphiphilicsiloxane-containing (meth)acrylamides having a polyethylene glycol(“PEG”) segment and a bulky siloxane group. The present invention isalso related to medical devices including contact lenses made from acomposition comprising an amphiphilic siloxane-containing(meth)acrylamide of the invention. In addition, the present invention isrelated to a method for making silicone hydrogel contact lenses.

BACKGROUND

In recent years, soft silicone hydrogel contact lenses become more andmore popular because of their high oxygen permeability and comfort.“Soft” contact lenses can conform closely to the shape of the eye, sooxygen cannot easily circumvent the lens. Soft contact lenses must allowoxygen from the surrounding air (i.e., oxygen) to reach the corneabecause the cornea does not receive oxygen from the blood supply likeother tissue. If sufficient oxygen does not reach the cornea, cornealswelling occurs. Extended periods of oxygen deprivation cause theundesirable growth of blood vessels in the cornea. By having high oxygenpermeability, a silicone hydrogel contact lens allows sufficient oxygenpermeate through the lens to the cornea and to have minimal adverseeffects on corneal health.

Typically, silicone hydrogel contact lenses are produced according to acast molding technique involving use of disposable or reusable molds anda silicone hydrogel lens formulation (i.e., a mixture of vinylicmonomers and/or vinylic macromers). A silicone hydrogel lens formulationoften comprises a bulky siloxane-containing vinylic monomer, such as,for example, a vinylic monomer having a tris(trialkylsilyloxy)silylalkylgroup (e.g., tris(trimethylsilyloxy)-silylpropyl acrylate,tris(trimethylsilyloxy)-silylpropyl methacrylate,tris(trimethylsilyloxy)-silylpropyl acryalmide,tris(trimethylsilyloxy)-silylpropyl methacrylamide,tris-(trimethylsiloxysilyl) propylvinyl carbamate, etc.). It is reportedthat such a bulky siloxane-containing vinylic monomer is critical to theelimination of optical defects derived from handling duringmanufacturing, especially when curing the monomer mixture in a moldwithin a relatively short time (e.g., less than about 300 seconds) witha UV light. When such a bulky siloxane-containing vinylic monomer iseliminated from a monomer mixture for making silicone hydrogel contactlenses, resultant lenses may develop permanent deformations (opticsdefects) due to handling. But, when such a bulky siloxane-containingvinylic monomer is present, resultant lenses exhibit a ‘healing’ effectthat eliminated the optical defects (i.e., the folding marks becometransient and can disappear after a short time period, e.g., about 15minutes or less).

However, most of available bulky-siloxane-containing vinylic monomersare hydrophobic and not suitable for making water-based siliconehydrogel lens formulations. In addition, unpolymerized bulkysiloxane-containing vinylic monomers must be removed from molded lensesby using an organic solvent in a lens extraction process. Such lensextraction process increases the production cost and is notenvironmentally friendly.

Therefore, there is still a need for amphiphilic siloxane-containingvinylic monomers which have adequate solubility in water and can be usedin an environmentally-friendly lens production process.

SUMMARY OF THE INVENTION

In one aspect, the invention provides an amphiphilic siloxane-containing(meth)acrylamide, which comprises one sole (meth)acrylamido group; onesole bulky siloxane group; and one hydrophilic polyethylene glycolsegment which is either a dangling polymer chain or a hydrophilic linkerbetween the (meth)acrylamido group and the bulky siloxane group.

The present invention, in another aspect, provides a polymer (preferablyan actinically-crosslinkable prepolymer or silicone hydrogel material)which is a polymerization product of a polymerizable compositioncomprising an amphiphilic siloxane-containing (meth)acrylamide of theinvention.

The present invention, in a further aspect, provides a medical device,preferably an ophthalmic device, more preferably a silicone hydrogelcontact lens, which comprises a polymeric material comprising monomericunits derived from an amphiphilic siloxane-containing (meth)acrylamideof the invention.

The present invention, in still a further aspect, provides a method forproducing silicone hydrogel contact lenses. The method comprises thesteps of: introducing a lens-forming formulation into a mold for makingcontact lenses, wherein the lens-forming formulation comprises (a) asolvent selected from the group consisting of water, 1,2-propyleneglycol, a polyethyleneglycol having a molecular weight of about 400Daltons or less, and mixtures thereof, (b) at least one amphiphilicsiloxane-containing (meth)acrylamide of the invention and/or at leastone actinically-crosslinkable prepolymer of the invention, and (c) atleast one component selected from the group consisting of a hydrophilicvinylic monomer, a hydrophilized polysiloxane-containing crosslinker, ahydrophilic crosslinker, a photoinitiator, a thermal initiator, aUV-absorbing vinylic monomer, a visibility tinting agent, anantimicrobial agent, a bioactive agent, a leachable lubricant, aleachable tear-stabilizing agent, and mixtures thereof; polymerizing thelens-forming formulation in the mold to form a silicone hydrogel contactlens, wherein the formed silicone hydrogel contact lens has a watercontent of from about 20% to about 75% (preferably from about 25% toabout 70%, more preferably from about 30% to about 65%) by weight whenfully hydrated, an oxygen permeability (Dk) of at least about 40 barrers(preferably at least about 50 barrers, more preferably at least about 60barrers, and even more preferably at least about 70 barrers), and anelastic modulus of from about 0.1 MPa to about 2.0 MPa, preferably fromabout 0.2 MPa to about 1.5 MPa, more preferably from about 0.3 MPa toabout 1.2 MPa, even more preferably from about 0.4 MPa to about 1.0 MPa.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Generally, the nomenclatureused herein and the laboratory procedures are well known and commonlyemployed in the art. Conventional methods are used for these procedures,such as those provided in the art and various general references. Wherea term is provided in the singular, the inventors also contemplate theplural of that term. The nomenclature used herein and the laboratoryprocedures described below are those well known and commonly employed inthe art.

“About” as used herein means that a number referred to as “about”comprises the recited number plus or minus 1-10% of that recited number.

A “medical device” refers to a device having surfaces that contacttissue, blood, or other bodily fluids of patients in the course of theiroperation. Exemplary medical devices include: (1) extracorporeal devicesfor use in surgery such as blood oxygenators, blood pumps, bloodsensors, tubing used to carry blood and the like which contact bloodwhich is then returned to the patient; (2) prostheses implanted in ahuman or animal body such as vascular grafts, stents, pacemaker leads,heart valves, and the like that are implanted in blood vessels or in theheart; (3) devices for temporary intravascular use such as catheters,guide wires, and the like which are placed into blood vessels or theheart for purposes of monitoring or repair; and (4) ophthalmic devices.

An “ophthalmic device”, as used herein, refers to a contact lens (hardor soft), an intraocular lens, a corneal onlay, other ophthalmic devices(e.g., stents, glaucoma shunt, or the like) used on or about the eye orocular vicinity.

“Contact Lens” refers to a structure that can be placed on or within awearer's eye. A contact lens can correct, improve, or alter a user'seyesight, but that need not be the case. A contact lens can be of anyappropriate material known in the art or later developed, and can be asoft lens, a hard lens, or a hybrid lens. A “silicone hydrogel contactlens” refers to a contact lens comprising a silicone hydrogel material.

A “hydrogel” or “hydrogel material” refers to a polymeric material whichis insoluble in water, but can absorb at least 10 percent by weight ofwater when it is fully hydrated.

A “silicone hydrogel” refers to a silicone-containing hydrogel obtainedby copolymerization of a polymerizable composition comprising at leastone silicone-containing monomer or at least one silicone-containingmacromer or at least one crosslinkable silicone-containing prepolymer.

“Hydrophilic,” as used herein, describes a material or portion thereofthat will more readily associate with water than with lipids.

A “vinylic monomer” refers to a compound that has one sole ethylenicallyunsaturated group and is soluble in a solvent.

The term “soluble”, in reference to a compound or material in a solvent,means that the compound or material can be dissolved in the solvent togive a solution with a concentration of at least about 1% by weight atroom temperature (i.e., a temperature of about 20° C. to about 30° C.).

The term “insoluble”, in reference to a compound or material in asolvent, means that the compound or material can be dissolved in thesolvent to give a solution with a concentration of less than 0.005% byweight at room temperature (as defined above).

As used in this application, the term “ethylenically unsaturated group”is employed herein in a broad sense and is intended to encompass anygroups containing at least one >C═C< group. Exemplary ethylenicallyunsaturated groups include without limitation (meth)acryloyl

allyl, vinyl, styrenyl, or other C═C containing groups.

As used in this application, the term “(meth)acrylamide” refers tomethacrylamide and/or acrylamide and the term “(meth)acrylate” refers tomethacrylate and/or acrylate.

As used herein, “actinically” in reference to curing, crosslinking orpolymerizing of a polymerizable composition, a prepolymer or a materialmeans that the curing (e.g., crosslinked and/or polymerized) isperformed by actinic irradiation, such as, for example, UV irradiation,ionizing radiation (e.g. gamma ray or X-ray irradiation), microwaveirradiation, and the like. Thermal curing or actinic curing methods arewell-known to a person skilled in the art.

As used in this application, the term “hydrophilic vinylic monomer”refers to a vinylic monomer capable of forming a homopolymer that iswater-soluble or can absorb at least 10 percent by weight water at roomtemperature.

As used in this application, the term “hydrophobic vinylic monomer”refers to a vinylic monomer which as a homopolymer typically yields apolymer that is insoluble in water and can absorb less than 10 percentby weight water at room temperature.

As used in this application, “TRIS” refers to a radical of—Si—[OSi(CH₃)₃]₃, namely the tris(trimethylsilyloxy)silyl group.

As used in this application, a “bulky siloxane group” refers to amonovalent radical of

in which B₁ is a trialkylsiloxy group of

A₁, A₂, A₃ and A₄ independent of one another are a C₁-C₆ alkyl, phenylor benzyl; and r1 is an integer of 2 or 3.

A “prepolymer” refers to a starting polymer which contains two or moreethylenically unsaturated groups and can be cured (e.g., crosslinked)actinically or thermally to obtain a crosslinked polymer having amolecular weight much higher than the starting polymer.

As used in this application, the term “crosslinker” refers to a compoundor polymer having at least two ethylenically unsaturated groups andbeing soluble in a solvent at room temperature. A “crosslinking agent”refers to a crosslinker having a molecular weight of about 700 Daltonsor less.

A “polysiloxane” refers to a compound containing one sole polysiloxanesegment of

in which R₁, R₂, R₃, R₄, R₅, R₆, R₇, and R₈ independently of oneanother, are C₁-C₁₀ alkyl, C₁-C₄ alkyl- or C₁-C₄-alkoxy-substitutedphenyl, C₁-C₁₀ fluoroalkyl, C₁-C₁₀ fluoroether, C₆-C₁₈ aryl radical,-alk-(OC₂H₄)_(n1)—OR9 in which alk is C₁-C₆-alkylene divalent radical,R₉ is H or C₁-C₄ alkyl and n1 is an integer from 1 to 10, m1 and m2independently of each other are an integer of from 0 to 50 and (m1+m2)is from 1 to 100.

A “chain-extended polysiloxane” refers to a compound containing at leasttwo polysiloxane segments separated by a linkage.

A “polysiloxane-containing crosslinker” refers to a compound having atleast two ethylenically unsaturated groups and at least one polysiloxanesegment.

As used in this application, the term “polymer” means a material formedby polymerizing/crosslinking one or more monomers or prepolymers.

As used in this application, the term “molecular weight” of a polymericmaterial (including monomeric or macromeric materials) refers to theweight-average molecular weight unless otherwise specifically noted orunless testing conditions indicate otherwise.

The term “alkyl” refers to a monovalent radical obtained by removing ahydrogen atom from a linear or branched alkane compound. An alkyl group(radical) forms one bond with one other group in an organic compound.

The term “alkylene” refers to a divalent radical obtained by removingone hydrogen atom from an alkyl. An alkylene group (or radical) formstwo bonds with other groups in an organic compound.

In this application, the term “substituted” in reference to an alkylenedivalent radical or an alkyl radical means that the alkylene divalentradical or the alkyl radical comprises at least one substituent whichreplaces one hydrogen atom of the alkylene or alkyl radical and isselected from the group consisting of hydroxyl, carboxyl, —NH₂,sulfhydryl, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio (alkyl sulfide),C₁-C₄ acylamino, C₁-C₄ alkylamino, di-C₁-C₄ alkylamino, halogen atom (Bror Cl), and combinations thereof.

The term “fluid” as used herein indicates that a material is capable offlowing like a liquid.

As used herein, the term “multiple” refers to three or more.

A free radical initiator can be either a photoinitiator or a thermalinitiator. A “photoinitiator” refers to a compound that initiates freeradical crosslinking/polymerizing reaction by the use of light. A“thermal initiator” refers to a compound that initiates radicalcrosslinking/polymerizing reaction by the use of heat energy.

A “UV-absorbing vinylic monomer” refers to a compound comprising anethylenically-unsaturated group and a UV-absorbing moiety which canabsorb or screen out UV radiation in the range from 200 nm to 400 nm asunderstood by a person skilled in the art.

A “spatial limitation of actinic radiation” refers to an act or processin which energy radiation in the form of rays is directed by, forexample, a mask or screen or combinations thereof, to impinge, in aspatially restricted manner, onto an area having a well definedperipheral boundary. A spatial limitation of UV radiation is obtained byusing a mask or screen having a radiation (e.g., UV) permeable region, aradiation (e.g., UV) impermeable region surrounding theradiation-permeable region, and a projection contour which is theboundary between the radiation-impermeable and radiation-permeableregions, as schematically illustrated in the drawings of U.S. Pat. No.6,800,225 (FIGS. 1-11), and U.S. Pat. No. 6,627,124 (FIGS. 1-9), U.S.Pat. No. 7,384,590 (FIGS. 1-6), and U.S. Pat. No. 7,387,759 (FIGS. 1-6),all of which are incorporated by reference in their entireties. The maskor screen allows to spatially projects a beam of radiation (e.g., UVradiation) having a cross-sectional profile defined by the projectioncontour of the mask or screen. The projected beam of radiation (e.g., UVradiation) limits radiation (e.g., UV radiation) impinging on alens-forming material located in the path of the projected beam from thefirst molding surface to the second molding surface of a mold. Theresultant contact lens comprises an anterior surface defined by thefirst molding surface, an opposite posterior surface defined by thesecond molding surface, and a lens edge defined by the sectional profileof the projected UV beam (i.e., a spatial limitation of radiation). Theradiation used for the crosslinking is radiation energy, especially UVradiation, gamma radiation, electron radiation or thermal radiation, theradiation energy preferably being in the form of a substantiallyparallel beam in order on the one hand to achieve good restriction andon the other hand efficient use of the energy.

The intrinsic “oxygen permeability”, Dk, of a material is the rate atwhich oxygen will pass through a material. As used in this application,the term “oxygen permeability (Dk)” in reference to a hydrogel (siliconeor non-silicone) or a contact lens means a measured oxygen permeability(Dk) which is corrected for the surface resistance to oxygen flux causedby the boundary layer effect according to the procedures shown inExamples hereinafter. Oxygen permeability is conventionally expressed inunits of barrers, where “barrer” is defined as [(cm³oxygen)(mm)/(cm²)(sec)(mm Hg)]×10⁻¹⁰.

The “oxygen transmissibility”, Dk/t, of a lens or material is the rateat which oxygen will pass through a specific lens or material with anaverage thickness of t [in units of mm] over the area being measured.Oxygen transmissibility is conventionally expressed in units ofbarrers/mm, where “barrers/mm” is defined as [(cm³ oxygen)/(cm²)(sec)(mmHg)]×10⁻⁹.

The term “water soluble or processable” in reference to a vinylicmonomer or a prepolymer of the invention means that the vinylic monomeror prepolymer has a water solubility and/or dispersity of from about 1%to about 70% by weight at room temperature (about 22° C. to about 28°C.).

The term “water solubility and/or dispersity” in reference to a vinylicmonomer or a prepolymer of the invention means the concentration (weightpercentage) of the vinylic monomer or prepolymer dissolved and/ordispersed in water at room temperature (about 22° C. to about 28° C.) toform a transparent aqueous solution or a slightly hazy aqueous solutionhaving a light transmissibility of 85% or greater in the range between400 to 700 nm.

A “coupling reaction” in this patent application is intended to describeany reaction between a pair of matching functional groups in thepresence or absence of a coupling agent to form covalent bonds orlinkages under various reaction conditions well known to a personskilled in the art, such as, for example, oxidation-reductionconditions, dehydration condensation conditions, addition conditions,substitution (or displacement) conditions, Diels-Alder reactionconditions, cationic crosslinking conditions, ring-opening conditions,epoxy hardening conditions, and combinations thereof.

Non-limiting examples of coupling reactions under various reactionconditions between a pair of matching co-reactive functional groupsselected from the group preferably consisting of amino group (—NHR′ inwhich R′ is H or C₁-C₄ alkyl), hydroxyl group, carboxyl group, acidhalide group (—COX, X=Cl, Br, or I), acid anhydrate group, aldehydegroup, azlactone group, isocyanate group, epoxy group, aziridine group,and thiol group, are given below for illustrative purposes. An aminogroup reacts with aldehyde group to form a Schiff base which may furtherbe reduced; an amino group NHR′ reacts with an acid chloride or bromidegroup or with an acid anhydride group to form an amide linkage (—CO—NR′—with R′ as defined above); an amino group NHR′ reacts with an isocyanategroup to form a urea linkage (—NR′—C(O)—NH— with R′ as defined above);an amino group NHR′ reacts with an epoxy or aziridine group to form anamine bond (—C—NR′— with R′ as defined above); an amino group NHR′reacts (ring-opening) with an azlactone group to form analkylene-diamido linkage (—C(O)NH-alkylene-C(O)NR′— with R′ as definedabove); an amino group NHR′ reacts with a carboxylic acid group in thepresence of a coupling agent carbodiimide (e.g.,1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC),N,N′-dicyclohexylcarbodiimide (DCC),1-cylcohexyl-3-(2-morpholinoethyl)carbodiimide, diisopropylcarbodiimide, or mixtures thereof) to form an amide linkage; an aminogroup NHR′ reacts with a N-hydroxysuccinimide ester group to form anamide linkage; a hydroxyl reacts with an isocyanate to form a urethanelinkage; a hydroxyl reacts with an epoxy or aziridine to form an etherlinkage (—O—); a hydroxyl reacts with an acid chloride or bromide groupor with an acid anhydride group to form an ester linkage; an hydroxylgroup reacts with an azlactone group in the presence of a catalyst toform an amidoalkylenecarboxy linkage (—C(O)NH-alkylene-C(O)—O—); acarboxyl group reacts with an epoxy group to form an ester bond; a thiolgroup (—SH) reacts with an isocyanate to form a thiocarbamate linkage(—N—C(O)—S—); a thiol group reacts with an epoxy or aziridine to form athioether linkage (—S—); a thiol group reacts with an acid chloride orbromide group or with an acid anhydride group to form a thiolesterlinkage; a thiol group reacts with an azlactone group in the presence ofa catalyst to form a linkage (—C(O)NH—CR₃R₄—(CH₂)p-C(O)—S—). A thiolgroup reacts with a vinyl group based on thiol-ene reaction underthiol-ene reaction conditions to form a thioether linkage (—S—). A thiolgroup reacts with an acryloyl or methacryloyl group based on MichaelAddition under appropriate reaction conditions to form a thioetherlinkage.

It is also understood that coupling agents with two reactive functionalgroups may be used in the coupling reactions. A coupling agent havingtwo reactive functional groups can be a diisocyanate, a di-acid halide,a di-carboxylic acid compound, a di-acid halide compound, a di-azlactonecompound, a di-epoxy compound, a diamine, or a diol. A person skilled inthe art knows well to select a coupling reaction (e.g., anyone describedabove in this application) and conditions thereof to prepare apolysiloxane terminated with one or more ethylenically unsaturatedgroups. For example, a diisocyanate, di-acid halide, di-carboxylic acid,di-azlactone, or di-epoxy compound can be used in the coupling of twohydroxyl, two amino groups, two carboxyl groups, two epoxy groups, orcombination thereof; a diamine or dihydroxyl compound can be used in thecoupling of two isocyanate, epoxy, aziridine, carboxylic acid, acidhalide or azlactone groups or combinations thereof.

Any suitable C₄-C₂₄ diisocyanates can be used in the invention. Examplesof preferred diisocyanates include without limitation isophoronediisocyanate, hexamethyl-1,6-diisocyanate, 4,4′-dicyclohexylmethanediisocyanate, toluene diisocyanate, 4,4′-diphenyl diisocyanate,4,4′-diphenylmethane diisocyanate, p-phenylene diisocyanate,1,4-phenylene 4,4′-diphenyl diisocyanate, 1,3-bis-(4,4′-isocyantomethyl) cyclohexane, cyclohexane diisocyanate, and combinations thereof.

Any suitable diamines can be used in the invention. An organic diaminecan be a linear or branched C₂-C₂₄ aliphatic diamine, a C₅-C₂₄cycloaliphatic or aliphatic-cycloaliphatic diamine, or a C₆-C₂₄ aromaticor alkyl-aromatic diamine. A preferred organic diamine isN,N′-bis(hydroxyethyl)ethylenediamine, N,N′-dimethylethylenediamine,ethylenediamine, N,N′-dimethyl-1,3-propanediamine,N,N′-diethyl-1,3-propanediamine, propane-1,3-diamine,butane-1,4-diamine, pentane-1,5-diamine, hexamethylenediamine, andisophorone diamine.

Any suitable diacid halides can be used in the invention. Examples ofpreferred diacid halide include without limitations fumaryl chloride,suberoyl chloride, succinyl chloride, phthaloyl chloride, isophthaloylchloride, terephthaloyl chloride, sebacoyl chloride, adipoyl chloride,trimethyladipoyl chloride, azelaoyl chloride, dodecanedioic acidchloride, succinic chloride, glutaric chloride, oxalyl chloride, dimeracid chloride, and combinations thereof.

Any suitable di-epoxy compounds can be used in the invention. Examplesof preferred di-epoxy compounds are neopentyl glycol diglycidyl ether,1,4-butanediol diglycidyl ether, 1,6-hexanediol diglycidyl ether,glycerol diglycidyl ether, ethylene glycol diglycidyl ether, diethyleneglycol diglycidyl ether, polyethylene glycol diglycidyl ether, propyleneglycol diglycidyl ether, dipropylene glycol diglycidyl ether, andcombinations thereof. Such di-epoxy compounds are available commercially(e.g., those DENACOL series di-epoxy compounds from Nagase ChemteXCorporation).

Any suitable C₂-C₂₄ diols (i.e., compounds with two hydroxyl groups) canbe used in the invention. Examples of preferred diols include withoutlimitation ethylene glycol, diethylene glycol, triethylene glycol,tetraethylene glycol, polyethylene glycol, propylene glycol,1,4-butanediol, various pentanediols, various hexanediols, variouscyclohexanediols, and combination thereof.

Any suitable C₃-C₂₄ di-carboxylic acid compounds can be used in theinvention. Examples of preferred di-carboxylic acid compounds includewithout limitation a linear or branched C₃-C₂₄ aliphatic dicarboxylicacid, a C₅-C₂₄ cycloaliphatic or aliphatic-cycloaliphatic dicarboxylicacid, a C₆-C₂₄ aromatic or araliphatic dicarboxylic acid, a dicarboxylicacid which contains amino or imido groups or N-heterocyclic rings, andcombinations thereof. Examples of suitable aliphatic dicarboxylic acidsare: oxalic acid, malonic acid, succinic acid, glutaric acid, adipicacid, pimelic acid, suberic acid, azelaic acid, sebacic acid,undecanedioic acid, dodecanedioic acid, dimethylmalonic acid,octadecylsuccinic acid, trimethyladipic acid, and dimeric acids(dimerisation products of unsaturated aliphatic carboxylic acids, suchas oleic acid). Examples of suitable cycloaliphatic dicarboxylic acidsare: 1,3-cyclobutanedicarboxylic acid, 1,3-cyclopentanedicarboxylicacid, 1,3- and 1,4-cyclohexanedicarboxylic acid, 1,3- and1,4-dicarboxylmethylcyclohexane, 4,4′-dicyclohexyldicarboxylic acid.Examples of suitable aromatic dicarboxylic acids are: terephthalic acid,isophthalic acid, o-phthalic acid, 1,3-, 1,4-, 2,6- or2,7-naphthalenedicarboxylic acids, 4,4′-diphenyldicarboxylic acid,4,4′-diphenylsulphone-dicarboxylic acid,1,1,3-trimethyl-5-carboxyl-3-(p-carboxyphenyl)-indane, 4,4′-diphenylether-dicarboxylic acid, bis-p-(carboxylphenyl)-methane.

Any suitable C₁₀-C₂₄ di-azlactone compounds can be used in theinvention. Examples of such diazlactone compounds are those described inU.S. Pat. No. 4,485,236 (herein incorporated by reference in itsentirety).

The reactions conditions for the above described coupling reactions aretaught in textbooks and are well known to a person skilled in the art.

The term “ethylenically functionize” or ethylenically functionalization”in reference to a compound or polymer or copolymer having one or morereactive functional groups (e.g., amine, hydroxyl, carboxyl, isocyanate,anhydride, and/or epoxy groups) means a process or product thereof inwhich one or more ethylenically unsaturated groups are covalentlyattached to the functional groups of the compound or polymer orcopolymer by reacting an ethylenically functionalizing vinylic monomerwith the compound or polymer or copolymer under coupling reactionconditions.

An “ethylenically functionalizing vinylic monomer” throughout of thispatent application refers to a vinylic monomer having one reactivefunctional group capable of participating in a coupling (orcrosslinking) reaction known to a person skilled in the art. Examples ofethylenically-functionalizing vinylic monomers include withoutlimitation C₂ to C₆ hydroxylalkyl (meth)acrylate, C₂ to C₆ hydroxyalkyl(meth)acrylamide, allylalcohol, allylamine, amino-C₂-C₆ alkyl(meth)acrylate, C₁-C₆ alkylamino-C₂-C₆ alkyl (meth)acrylate, vinylamine,amino-C₂-C₆ alkyl (meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl(meth)acrylamide, acrylic acid, C₁-C₄ alkylacrylic acid (e.g.,methacrylic ethylacrylic acid, propylacrylic acid, butylacrylic acid),N-[tris(hydroxymethyl)-methyl]acrylamide, N,N-2-acrylamidoglycolic acid,beta methyl-acrylic acid (crotonic acid), alpha-phenyl acrylic acid,beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid,1-carboxy-4-phenyl butadiene-1,3, itaconic acid, citraconic acid,mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaricacid, aziridinyl C₁-C₁₂ alkyl (meth)acrylate (e.g., 2-(1-aziridinyl)ethyl (meth)acrylate, 3-(1-aziridinyl) propyl (meth)acrylate,4-(1-aziridinyl) butyl (meth)acrylate, 6-(1-aziridinyl) hexyl(meth)acrylate, or 8-(1-aziridinyl) octyl (meth)acrylate), glycidyl(meth)acrylate, vinyl glycidyl ether, allyl glycidyl ether,(meth)acryloyl halide groups (CH₂═CH—COX or CH₂═CCH₃—COX, X=Cl or Br),N-hydroxysuccinimide ester of (meth)acrylic acid, C₁ to C₆isocyanatoalkyl (meth)acrylate, azlactone-containing vinylic monomers(e.g., 2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one,2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one,2-vinyl-4-methyl-4-ethyl-1,3-oxazolin-5-one,2-isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one,2-vinyl-4,4-dibutyl-1,3-oxazolin-5-one,2-isopropenyl-4-methyl-4-dodecyl-1,3-oxazolin-5-one,2-isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one,2-isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one,2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one,2-vinyl-4,4-diethyl-1,3-oxazolin-5-one,2-vinyl-4-methyl-4-nonyl-1,3-oxazolin-5-one,2-isopropenyl-4-methyl-4-phenyl-1,3-oxazolin-5-one,2-isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one,2-vinyl-4,4-pentamethylene-1,3-oxazolin-5-one, and2-vinyl-4,4-dimethyl-1,3-oxazolin-6-one, with2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one (VDMO) and2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one (IPDMO) as preferredazlactone-containing vinylic monomers), and combinations thereof.

In general, the invention is directed to a class of amphiphilicsiloxane-containing (meth)acrylamides and uses in preparing a polymer(preferably an actinically-crosslinkable prepolymer or silicone hydrogelmaterial) and in producing a medical device (preferably an ophthalmicdevices, more preferably a silicone hydrogel contact lens). Anamphiphilic siloxane-containing (meth)acrylamide of the inventioncomprises: one sole (meth)acrylamido group (preferably acrylamidogroup); one sole TRIS group; and one hydrophilic polyethylene glycolsegment which is either a dangling polymer chain or a hydrophilic linkerbetween the (meth)acrylamido group and the TRIS group. It is believedthat an amphiphilic TRIS-containing (meth)acrylamide of the inventionhas an adequate solubility in water largely because of its hydrophilicpolyethylene glycol segment present in the monomer. It can be used in amanufacturing process for making silicone hydrogel contact lenses in amore environmentally-friendly manner (e.g., using a water-based lensformulation and/or lens extraction with water). Further, a(meth)acrylamido group is less susceptible to hydrolysis than a(meth)acryloyloxy group while is more hydrophilic than a(meth)acryloyloxy group. In addition, because a (meth)acrylamide has ahigher reactivity than a (meth)acrylate, a Tris-containing(meth)acrylamide of the invention is more suitable for aUV-polymerization process requiring a short curing time (e.g., within atime period of about 50 seconds or less).

The present invention, in one aspect, provides an amphiphilicsiloxane-containing (meth)acrylamide being represented by formula (1) or(2)

in which

-   -   A₁, A₂, A₃ and A₄ independent of one another are a C₁-C₆ alkyl        (preferably methyl), phenyl or benzyl,    -   r1 is an integer of 2 or 3,    -   R′ is H or C₁-C₄ alkyl,    -   R₁₀ is hydrogen or methyl,    -   R₁₁ is a linear or branched C₂-C₆ alkylene divalent radical        which may be substituted with one or more hydroxyl groups,    -   R₁₂ is C₁-C₄ alkoxy,    -   Z₁ and Z₂ independent of each another are a direct bond or a        linear or branched C₁-C₄ alkylene divalent radical,    -   Z₃ is C₂-C₄ alkylene divalent radical,    -   Z₄, Z₅, and Z₆ independent of one another are a direct bond or a        linear or branched C₁-C₂₀ alkylene divalent radical which may        have one or more ether, thio, amine, carbonyl, or amido linkages        in their main chain,    -   X₁ is —O—CO—NH— or —O—CO—NH—R₁₃—NH—CO—O— in which R₁₃ is a        linear or branched C₂-C₁₂ alkylene divalent radical or a C₅-C₄₅        cycloaliphatic or aliphatic-cycloaliphatic divalent radical,    -   X₂ and X₃ independent of each other are selected from the group        consisting of direct bond, —O—, —NR′—, —CO—NR′—, —NR′—CO—,        —O—CO—NH—, —NH—CO—O—, —NR′—CO—NH—, —NH—CO—NR′—, —S—CO—NH—,        —NH—CO—S—, —S—, —CO—O—, —O—CO—, —O—CO—NH—R₁₃—NH—CO—O—, and        —NH—CO—NH—R₁₃—NH—CO—NH—, in which R′ and R₁₃ are as defined        above, q1 is an integer from 2 to 50, q2 is an integer from 3 to        20.

In a preferred embodiment, an amphiphilic siloxane-containing(meth)acrylamide of the invention is represented by formula (1) inwhich: R′ is hydrogen; R₁₀ is hydrogen or methyl; R₁₁ is a linear orbranched C₂-C₆ alkylene divalent radical; R₁₂ is C₁-C₆ alkoxy; Z₁ and Z₂are a direct bond; Z₃ is C₂-C₄ alkylene divalent radical; X₁ is—O—CO—NH— or —O—CO—NH—R₁₃—NH—CO—O— in which R₁₃ is a linear or branchedC₂-C₁₂ alkylene divalent radical or a C₅-C₄₅ cycloaliphatic oraliphatic-cycloaliphatic divalent radical; q1 is an integer from 2 to50.

In a preferred embodiment, an amphiphilic siloxane-containing(meth)acrylamide of the invention is represented by any one of formula(2a) to (2d)

in which: R₁₀ is hydrogen or methyl; R₁₁ is a linear or branched C₂-C₆alkylene divalent radical; R₁₄ is —CH₂CH₂CH₂— or —CH₂CH(CH₃)—; X₄ and X₆independent of each other are —O—, —NH—, —CO—NH—, —NH—CO—, —O—CO—NH—,—NH—CO—NH—, —CO—O—, —O—CO—, —S—, —O—CO—NH—R₁₃—NH—CO—O—, or—NH—CO—NH—R₁₃—NH—CO—NH— in which R₁₃ is a linear or branched C₂-C₁₂alkylene divalent radical or a C₅-C₄₅ cycloaliphatic oraliphatic-cycloaliphatic divalent radical; X₅ is —NH—, —CO—NH—, —NH—CO—,—NH—CO—NH—, —CO—O—, —O—CO—, —S—, or —NH—CO—NH—R₁₃—NH—CO—NH— in which R₁₃is a linear or branched C₂-C₁₂ alkylene divalent radical or a C₅-C₄₅cycloaliphatic or aliphatic-cycloaliphatic divalent radical; q2 is aninteger from 2 to 50; n1 and n3 independent of each other are an integerfrom 1 to 3; n2 is an integer 2 or 3.

An amphiphilic siloxane-containing (meth)acrylamide of formula (1) canbe prepared from the following starting materials: (1) a(meth)acrylamide having one carboxyl (—COOH) group and one hydroxy (—OH)group (e.g., (meth)acrylamido glycolic acid or the like); (2) anisocyanatoalkly- or hydroxyalkyl-tris(trimethylsiloxy)silane or anisocyanato- or hydroxy-containing bulky silane (e.g., OCN—R₁₁-TRIS,HO—R₁₁-TRIS, OCN—R₁₁—Si(B₁)_(r1)(A₁)_(3-r1),HO—R₁₁—Si(B₁)_(r1)(A₁)_(3-r1) in which A₁, B₁ and r1 are as definedabove, or the like); (3) mono-amine or mono-carboxy terminatedpolyethylene glycol (i.e., NH₂-PEG-OR₁₂ or HOOC-PEG-OR₁₂) according tocoupling methods known to a person skilled in the art. As anillustrative example, Scheme I shows an illustrative scheme forpreparing an amphiphilic siloxane-containing (meth)acrylamide of formula(1).

It should be understood that HOOC-PEG-OR₁₂ can substitute NH₂-PEG-OR₁₂at step II and reacts with (meth)acrylamido glycolic acidN-hydroxysuccinimide ester in the presence of a diamine coupling agent(any one of those described above) to form a diamide linkage (instead ofone sole amide linkage as shown in Scheme I). Similarly,OCN—R₁₁—Si(B₁)_(r1)(A₁)_(3-r1) can substitute OCN—R₁₁-TRIS at step IIIand reacts with the reaction product of step II; and HO—R₁₁-TRIS orHO—R₁₁—Si(B₁)_(r1)(A₁)_(3-r1) can substitute OCN—R₁₁-TRIS at step IIIand reacts with the reaction product of step II in the presence of adiisocyanate coupling agent (any one of those described above) to form adiurethane linkage (instead of one sole urethane linkage as shown inScheme I).

Alternatively, an amphiphilic siloxane-containing (meth)acrylamide offormula (1) can be prepared from the following starting materials: (1) acompound having one amino group (—NHR′ with R′ as defined above), onecarboxyl group and one hydroxy group (e.g., serine, threonine,L-β-Homoserine, L-β-homothreonine, L-β-Homohydroxyproline, or the like);(2) (meth)acrylic acid N-hydroxysuccinimide ester (commerciallyavailable from Sigma-Aldrich); (3) an isocyanatoalkly- or bromo- orchloro-alkyl- or hydroxyalkyl-tris(trimethylsiloxy)silane or anisocyanatoalkly- or bromo- or chloro-alkyl- or hydroxyalkyl-containingbulky silane; (4) mono-functional polyethylene glycol according tocoupling methods known to a person skilled in the art. As anillustrative example, Scheme II shows another illustrative scheme forpreparing an amphiphilic siloxane-containing (meth)acrylamide of formula(1) from serine.

It is understood that serine can be replaced by threonine,L-β-Homoserine, L-β-homothreonine, L-β-Homohydroxyproline in Scheme IIfor preparing an amphiphilic siloxane-containing (meth)acrylamide offormula (1). HOOC-PEG-OR₁₂ can substitute NH₂-PEG-OR₁₂ at step III andreacts with the reaction product of step II in the presence of a diaminecoupling agent (any one of those described above) to form a diamidelinkage (instead of one sole amide linkage as shown in Scheme II).Similarly, OCN—R₁₁—Si(B₁)_(r1)(A₁)_(3-r1) can substitute OCN—R₁₁-TRIS atstep IV and reacts with the reaction product of step III; andHO—R₁₁-TRIS or HO—R₁₁—Si(B₁)_(r1)(A₁)_(3-r1) can substitute OCN—R₁₁-TRISat step IV and reacts with the reaction product of step III in thepresence of a diisocyanate coupling agent (any one of those describedabove) to form a diurethane linkage (instead of one sole urethanelinkage as shown in Scheme II).

An amphiphilic siloxane-containing (meth)acrylamide of formula (2) canbe prepared from the following starting materials: (1) anamino-containing or carboxy-containing (meth)acrylamide (e.g.,N-(2-aminoethyl)methacrylamide hydrochloride, N-(3-aminopropyl)methacrylamide hydrochloride, N-(2-carboxypropyl)methacrylamide(2-CPMA), N-(3-carboxypropyl)methacrylamide (3-CPMA),N,N-2-acrylamidoglycolic acid, or the like); (2) a heterobifunctionalpolyethylene glycol (e.g., HO-PEG-COOH, HO-PEG-NH₂, NH₂-PEG-COOH,HS-PEG-COOH, HS-PEG-NH₂, Boc-NH-PEG-NHS, Boc-NH-PEG-NH₂, Boc-NH-PEG-NHS,in which Boc stands for amino protecting group—tert-Butyl carbamate, allof which are available from Creative PEGWORKs); (3) atris(trimethylsiloxy)silane having a reactive functional group selectedfrom the group consisting of amino, carboxy, isocyanato, and hydroxygroup (e.g., aminopropyl-tris(trimethylsiloxy)silane,isocyanatopropyl-tris(trimethylsiloxy)silane,hydroxyethoxypropyl-tris(trimethylsiloxy)silane,chloropropyl-tris(trimethylsiloxy)silane, the Michael reaction productof carboxy-containing mercaptane (e.g., 2-mercaptopropinic acid,thioglycolic acid, thiolactic acid, or the like) with vinyltris(trimethylsiloxy)silane).

As an illustrative example, Scheme III shows an illustrative scheme forpreparing an amphiphilic siloxane-containing (meth)acrylamide of formula(2a).

It is understood that NH₂-PEG-COOH can be replaced by NH₂-PEG-OH orNH₂-PEG-SH or NH₂-PEG-NH-Boc in Scheme III step I to obtain a(meth)acrylamido-terminated, hydroxy-terminated (or HS-terminated orBoc-terminated polyethylene glycol). Where the functional group of thereaction product of step I in Scheme III is hydroxy group, it can reactwith an isocyanatoalkyl tris(trimethylsiloxy)silane to form a(meth)acrylamide of formula (2a), or alternatively it can reacts withhydroxyethoxypropyl tris(trimethylsiloxy)silane in the presence of adiisocyanate coupling agent (any one of those described above) undercoupling reaction conditions (Tin catalyst, heating). Where thefunctional group of the reaction product of step I in Scheme III is Boc,Boc can be removed to recover NH₂ group which then can react with anisocyanatoalkyl tris(trimethylsiloxy)silane, with a carboxy-containingtris(trimethylsiloxy)silane in the presence of EDC andhydroxysuccinimide (HO—NHS), or withaminoalkyl-tris(trimethylsiloxy)silane in the presence of a diacidcoupling agent (anyone of those described above) or a diacid chloride(anyone of those described above) or a diisocyanate coupling agent (anyone of those described above) under coupling reaction conditions (Tincatalyst, heating), to form a (meth)acrylamide of formula (2a). Wherethe functional group of the reaction product of step I in Scheme III isthiol group, it can react with an isocyanatoalkyltris(trimethylsiloxy)silane or with a vinyl tris(trimethylsiloxy)silaneunder Michael Addition reaction conditions, to form a (meth)acrylamideof formula (2a).

Scheme IV illustrate a scheme for preparing an amphiphilicsiloxane-containing (meth)acrylamide of formula (2b).

It is understood that NH₂-PEG-COOH can be replaced by NH₂-PEG-NH-Boc orNH₂-PEG-SH in Scheme IV step I to obtain a (meth)acrylamido-terminated,Boc-terminated (or HS-terminated) polyethylene glycol. Where thefunctional group of the reaction product of step I in Scheme IV is Boc,Boc can be removed to recover NH₂ group which then can react with anisocyanatoalkyl tris(trimethylsiloxy)silane or with a carboxy-containingtris(trimethylsiloxy)silane in the presence of EDC andhydroxysuccinimide (HO—NHS), or withaminoalkyl-tris(trimethylsiloxy)silane in the presence of a diacidcoupling agent (anyone of those described above) or a diisocyanatecoupling agent (any one of those described above) under couplingreaction conditions, to form a (meth)acrylamide of formula (2b). Wherethe functional group of the reaction product of step I in Scheme IV isthiol group, it can react with an isocyanatoalkyltris(trimethylsiloxy)silane or with a vinyl tris(trimethylsiloxy)silaneunder Michael Addition reaction conditions, to form a (meth)acrylamideof formula (2b).

Scheme V illustrates a scheme for preparing an amphiphilicsiloxane-containing (meth)acrylamide of formula (2c).

It is understood that HO-PEG-NHS can be replaced by NHS-PEG-NH-Boc orNHS-PEG-SH in Scheme V step I to obtain a (meth)acrylamido-terminated,Boc-terminated (or HS-terminated) polyethylene glycol. Where thefunctional group of the reaction product of step I in Scheme V is Boc,Boc can be removed by well-known hydrolysis to recover NH₂ group whichthen can react with an isocyanatoalkyl tris(trimethylsiloxy)silane orwith a carboxy-containing tris(trimethylsiloxy)silane in the presence ofEDC and N-hydroxysuccinimide (HO—NHS), or withaminoalkyl-tris(trimethylsiloxy)silane in the presence of a diacidcoupling agent (anyone of those described above) or a diisocyanatecoupling agent (any one of those described above) under couplingreaction conditions, to form a (meth)acrylamide of formula (2c). Wherethe functional group of the reaction product of step I in Scheme V isthiol group, it can react with an isocyanatoalkyltris(trimethylsiloxy)silane or with a vinyl tris(trimethylsiloxy)silaneunder Michael Addition reaction conditions, to form a (meth)acrylamideof formula (2c).

An amphiphilic siloxane-containing (meth)acrylamide of formula (2d) canbe prepared according to Scheme IV from any carboxy-containing(meth)acrylamide (e.g., N-(2-carboxypropyl)methacrylamide (2-CPMA),N-(3-carboxypropyl)methacrylamide (3-CPMA)) which replaces(meth)acrylamido glycolic acid in Scheme IV.

In a preferred embodiment, an amphiphilic siloxane-containing(meth)acrylamide of any one of formula (1), (2), and (2a) to (2d) has awater solubility or dispersibility of at least about 5%, preferably atleast about 10%, more preferably at least about 20% by weight in water.

An amphiphilic siloxane-containing (meth)acrylamide of formula (1) or(2) (including those preferred embodiments described above) as definedabove can find particular use in preparing a polymer, preferably asilicone-containing actinically-crosslinkable prepolymer or a siliconehydrogel polymeric material, which is another aspect of the invention. Aperson skilled in the art knows how to prepare a polymer, anactinically-crosslinkable silicone containing prepolymer, or a siliconehydrogel polymeric material from a polymerizable composition accordingto any known polymerization mechanism.

In this aspect of the invention, a polymer can be a copolymer soluble orinsoluble in a solvent, preferably an actinically-crosslinkableprepolymer or a silicone hydrogel material.

Various embodiments of amphiphilic siloxane containing vinylic monomersof formula (I) can be used in a polymerizable composition for preparinga polymer, a prepolymer or a silicone hydrogel material of theinvention. It is understood that a polymerizable composition forpreparing a polymer, an actinically-crosslinkable silicone-containingprepolymer or a silicone hydrogel polymeric material of the inventionmay optionally comprise a hydrophilized siloxane-containing(meth)acrylamide having at least one hydrophilic moiety selected fromthe group consisting of a short hydrophilic polymeric chain with amolecular weight of up to about 1000 Daltons (preferably about 800Dalton or less, even more preferably about 500 Daltons or less), apendant hydroxyl group, an amide linkage, a urethane linkage (orcarbamate linkage), a diurethane linkage, a 2-hydroxy-substitutedpropyleneoxide linkage, and combinations thereof. Examples ofhydrophilized siloxane-containing vinylic monomers include withoutlimitation those described in U.S. Pat. Nos. 4,711,943, 5,070,215,5,760,100 (Macromer C), 5,981,615, 5,998,498, 7,071,274, 7,112,641,8,071,703, 8,044,111, and 8,048,968; in PCT patent applicationpublication WO0059970; and in US patent application Nos. 2010/0120939A1, 2010/0298446 A1, 2012/0088843 A1, 2012/0088844 A1, and 2012/0088861A1, all of which are herein incorporated by reference in theirentireties.

A person skilled in the art knows how to prepare a polymer, anactinically-crosslinkable silicone-containing prepolymer, or a siliconehydrogel material from a polymerizable composition according to anyknown free-radical polymerization mechanism. The polymerizablecomposition for preparing a polymer, an intermediary copolymer forpreparing an actinically-crosslinkable silicone containing prepolymer,or a silicone hydrogel polymeric material of the invention can be amelt, a solventless liquid in which all necessary components are blendedtogether, or a solution in which all necessary component is dissolved inan inert solvent, such as water, an organic solvent, or mixture thereof,as known to a person skilled in the art.

Example of suitable solvents includes without limitation, water,tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycolmethyl ether, ethylene glycol n-butyl ether, ketones (e.g., acetone,methyl ethyl ketone, etc.), diethylene glycol n-butyl ether, diethyleneglycol methyl ether, ethylene glycol phenyl ether, propylene glycolmethyl ether, propylene glycol methyl ether acetate, dipropylene glycolmethyl ether acetate, propylene glycol n-propyl ether, dipropyleneglycol n-propyl ether, tripropylene glycol n-butyl ether, propyleneglycol n-butyl ether, dipropylene glycol n-butyl ether, tripropyleneglycol n-butyl ether, propylene glycol phenyl ether dipropylene glycoldimetyl ether, polyethylene glycols, polypropylene glycols, ethylacetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate,i-propyl lactate, methylene chloride, 2-butanol, 1-propanol, 2-propanol,menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol,3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol,2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol,tert-amyl, alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol,3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol,3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol,2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2-methyl-2-nonanol,2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol,4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol,3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol,3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol,4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol,1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol,3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol,2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol,2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol,1-ethoxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol, isopropanol,1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethyl formamide,dimethyl acetamide, dimethyl propionamide, N-methyl pyrrolidinone, andmixtures thereof.

The copolymerization of a polymerizable composition for preparing apolymer, an actinically-crosslinkable silicone containing prepolymer(i.e., an intermediary copolymer for the prepolymer), or a siliconehydrogel polymeric material of the invention may be inducedphotochemically or thermally.

Suitable photoinitiators are benzoin methyl ether, diethoxyacetophenone,a benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone and Darocurand Irgacure types, preferably Darocur 1173®, Irgacure 369®, Irgacure379®, and Irgacure 2959®. Examples of benzoylphosphine oxide initiatorsinclude 2,4,6-trimethylbenzoyldiphenylophosphine oxide (TPO);bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide; andbis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Reactivephotoinitiators which can be incorporated, for example, into a macromeror can be used as a special monomer are also suitable. Examples ofreactive photoinitiators are those disclosed in EP 632 329, hereinincorporated by reference in its entirety. The polymerization can thenbe triggered off by actinic radiation, for example light, in particularUV light of a suitable wavelength. The spectral requirements can becontrolled accordingly, if appropriate, by addition of suitablephotosensitizers.

Suitable thermal polymerization initiators are known to the skilledartisan and comprise, for example peroxides, hydroperoxides,azo-bis(alkyl- or cycloalkylnitriles), persulfates, percarbonates ormixtures thereof. Examples are benzoylperoxide, tert.-butyl peroxide,di-tert.-butyl-diperoxyphthalate, tert.-butyl hydroperoxide,azo-bis(isobutyronitrile) (AlBN), 1,1-azodiisobutyramidine,1,1′-azo-bis(1-cyclohexanecarbonitrile),2,2′-azo-bis(2,4-dimethyl-valeronitrile) and the like. Thepolymerization is carried out conveniently in an above-mentioned solventat elevated temperature, for example at a temperature of from 25 to 100°C. and preferably 40 to 80° C. The reaction time may vary within widelimits, but is conveniently, for example, from 1 to 24 hours orpreferably from 2 to 12 hours. It is advantageous to previously degasthe components and solvents used in the polymerization reaction and tocarry out said copolymerization reaction under an inert atmosphere, forexample under a nitrogen or argon atmosphere.

Generally, a polymer of the invention is obtained by polymerizingthermally or actinically a polymerizable composition including anamphiphilic siloxane-containing (meth)acrylamide of formula (1) or (2)as defined above and one or more polymerizable components selected fromthe group consisting of a hydrophilic vinylic monomer, a hydrophobicvinylic monomer, a polysiloxane-containing vinylic monomer, apolysiloxane-containing crosslinker, a non-silicone crosslinker, ahydrophilic prepolymer, a UV-absorbing vinylic monomer, and combinationsthereof. Various embodiments of all of the above-described polymerizablecomponents are discussed below.

In accordance with the invention, any suitable hydrophilic vinylicmonomers can be used in a polymerizable composition for preparing apolymer of the invention. Examples of preferred hydrophilic vinylicmonomers include without limitation N-vinylpyrrolidone, N,N-dimethyl(meth)acrylamide, (meth)acrylamide, hydroxylethyl (meth)acrylamide,hydroxyethyl (meth)acrylate, glycerol methacrylate (GMA), polyethyleneglycol (meth)acrylate, polyethylene glycol C₁-C₄-alkyl ether(meth)acrylate having a weight average molecular weight of up to 1500,N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide,N-vinyl-N-methyl acetamide, N-methyl-3-methylene-2-pyrrolidone,1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone,5-ethyl-3-methylene-2-pyrrolidone, (meth)acrylic acid, ethylacrylicacid, and combinations thereof.

Any suitable hydrophobic vinylic monomers can be used in a polymerizablecomposition for making a polymer of the invention. By incorporating acertain amount of hydrophobic vinylic monomer in a monomer mixture, themechanical properties (e.g., modulus of elasticity) of the resultantpolymer may be improved. Examples of preferred hydrophobic vinylicmonomers include methylacrylate, ethyl-acrylate, propylacrylate,isopropylacrylate, cyclohexylacrylate, 2-ethylhexylacrylate,methylmethacrylate, ethylmethacrylate, propylmethacrylate, vinylacetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene,chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile,1-butene, butadiene, methacrylonitrile, vinyl toluene, vinyl ethylether, perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate,isobornyl methacrylate, trifluoroethyl methacrylate,hexafluoro-isopropyl methacrylate, hexafluorobutyl methacrylate.

Any suitable polysiloxane-containing (meth)acrylamide (each comprisingat least one polysiloxane segment and one sole ethylenically unsaturatedgroup) can be used in a polymerizable composition for preparing apolymer of the invention. Preferred examples of such vinylic monomersare mono-(meth)acrylated polydimethylsiloxanes of various molecularweight (e.g., mono-3-methacryloxypropyl terminated, mono-C₁-C₄ alkylterminated polydimethylsiloxane, ormono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated, mono-C₁-C₄alkyl terminated polydimethylsiloxane). Alternatively, monoethylenicallyfunctionalized polysiloxanes can be obtained by ethylenicallyfunctionalizing of a monofunctionalized polysiloxanes (i.e., with onesole terminal functional group, such as, e.g., —NH₂, —OH, —COOH, epoxygroup, halide, etc.) as described above. Suitable monofunctionalizedpolysiloxanes are commercially available, e.g., from Aldrich, ABCR GmbH& Co., Fluorochem, or Gelest, Inc, Morrisville, Pa.

Any suitable polysiloxane-containing crosslinkers (each of whichcomprises at least one polysiloxane segment and at least twoethylenically unsaturated groups) can be used in a polymerizablecomposition for preparing a polymer of the invention. Examples ofpolysiloxane-containing crosslinkers include without limitation,bis-(meth)acrylated polydimethylsiloxanes; bis-vinylcarbonate-terminated polydimethylsiloxanes; bis-vinylcarbamate-terminated polydimethylsiloxane; bis-vinyl terminatedpolydimethylsiloxanes; bis-(meth)acrylamide-terminatedpolydimethylsiloxanes; bis-3-methacryloxy-2-hydroxypropyloxypropylpolydimethylsiloxane;N,N,N′,N′-tetrakis(3-methacryloxy-2-hydroxypropyl)-alpha,omega-bis-3-aminopropyl-polydimethylsiloxane;polysiloxane or chain-extended polysiloxane crosslinkers selected fromthe group consisting of Macromer A, Macromer B, Macromer C, and MacromerD described in U.S. Pat. No. 5,760,100 (herein incorporated by referencein its entirety); the reaction products of glycidyl (meth)acrylate withbis-aminoalkyl-terminated or bis-hydroxyalkoxyalkyl terminatedpolydimethylsiloxanes; the reaction products of hydroxy-containing oramino-containing vinylic monomer with bis-epoxyalkoxyalkyl-terminatedpolydimethylsiloxanes; polysiloxane-containing crosslinkers disclosed inU.S. Pat. Nos. 4,136,250, 4,153,641, 4,182,822, 4,189,546, 4,259,467,4,260,725, 4,261,875, 4,343,927, 4,254,248, 4,355,147, 4,276,402,4,327,203, 4,341,889, 4,486,577, 4,543,398, 4,605,712, 4,661,575,4,684,538, 4,703,097, 4,833,218, 4,837,289, 4,954,586, 4,954,587,5,010,141, 5,034,461, 5,070,170, 5,079,319, 5,039,761, 5,346,946,5,358,995, 5,387,632, 5,416,132, 5,451,617, 5,486,579, 5,962,548,5,981,675, 6,039,913, 6,762,264, 7,091,283, 7,238,750, 7,268,189,7,566,754, 7,956,135, 8,071,696, 8,071,703, 8,071,658, 8,048,968, 8,283,429, 8,263,679, 8,044,111, and 8,211,955 and in published US patentapplication Nos. 2008/0015315 A1, 2010/0120939 A1, 2010/0298446 A1,2010/0296049 A1, 2011/0063567 A1, 2012/0088843 A1, 2012/0088844 A1,2012/0029111 A1, and 2012/0088861 A1 (herein incorporated by referencein their entireties). In a preferred embodiment, apolysiloxane-containing crosslinker used in a polymerizable compositionfor preparing a polymer, an anctinically-crosslinkable siliconecontaining prepolymer, or a silicone hydrogel polymeric material of theinvention is hydrophilized, namely a crosslinker containing at least onepolysiloxane segment and at least one pendant hydrophilic polymer chain.Examples of hydrophilized polysiloxane-containing crosslinkers includewithout limitation those described in US patent application Nos.2010/0120939 A1, 2010/0298446 A1, 2012/0088843 A1, 2012/0088844 A1, and2012/0088861 A1, all of which are herein incorporated by reference intheir entireties.

Any suitable non-silicone crosslinkers can be used in a polymerizablecomposition for preparing a polymer of the invention. Examples ofpreferred non-silicone crosslinkers include without limitationtetraethyleneglycol di-(meth)acrylate, triethyleneglycoldi-(meth)acrylate, ethyleneglycol di-(meth)acrylate, diethyleneglycoldi-(meth)acrylate, bisphenol A dimethacrylate, vinyl methacrylate,ethylenediamine di(meth)acrylamide, glycerol dimethacrylate,allyl(meth)acrylate, N,N′-methylenebis(meth)acrylamide,N,N′-ethylenebis(meth)acrylamide, N,N′-dihydroxyethylenebis(meth)acrylamide, a product of diamine (preferably selected from thegroup consisting of N,N′-bis(hydroxyethyl)ethylenediamine,N,N′-dimethylethylenediamine, ethylenediamine,N,N′-dimethyl-1,3-propanediamine, N,N′-diethyl-1,3-propanediamine,propane-1,3-diamine, butane-1,4-diamine, pentane-1,5-diamine,hexamethylenediamine, isophorone diamine, and combinations thereof) andepoxy-containing vinylic monomer (preferably selected from the groupconsisting of glycidyl (meth)acrylate, vinyl glycidyl ether, allylglycidyl ether, and combinations thereof), combinations thereof. A morepreferred crosslinker to be used in the preparation of a polymer, anactinically-crosslinkable silicone containing prepolymer, or a siliconehydrogel polymeric material of the invention is a hydrophiliccrosslinker selected from the group consisting oftetra(ethyleneglycol)diacrylate, tri(ethyleneglycol)diacrylate,ethyleneglycol diacrylate, di(ethyleneglycol)diacrylate, glyceroldimethacrylate, allyl(meth)acrylate, N,N′-methylene bis(meth)acrylamide,N,N′-ethylene bis(meth)acrylamide, N,N′-dihydroxyethylenebis(meth)acrylamide, and combinations thereof.

Examples of hydrophilic prepolymers with multiple acryloyl ormethacryloyl groups include, but are not limited to, a water-solublecrosslinkable poly(vinyl alcohol) prepolymer described in U.S. Pat. Nos.5,583,163 and 6,303,687; a water-soluble vinyl group-terminatedpolyurethane prepolymer described in U.S. Patent Application PublicationNo. 2004/0082680; derivatives of a polyvinyl alcohol, polyethyleneimineor polyvinylamine, which are disclosed in U.S. Pat. No. 5,849,841; awater-soluble crosslinkable polyurea prepolymer described in U.S. Pat.No. 6,479,587 and in U.S. Published Application No. 2005/0113549;crosslinkable polyacrylamide; crosslinkable statistical copolymers ofvinyl lactam, MMA and a comonomer, which are disclosed in EP 655,470 andU.S. Pat. No. 5,712,356; crosslinkable copolymers of vinyl lactam, vinylacetate and vinyl alcohol, which are disclosed in EP 712,867 and U.S.Pat. No. 5,665,840; polyether-polyester copolymers with crosslinkableside chains which are disclosed in EP 932,635 and U.S. Pat. No.6,492,478; branched polyalkylene glycol-urethane prepolymers disclosedin EP 958,315 and U.S. Pat. No. 6,165,408; polyalkyleneglycol-tetra(meth)acrylate prepolymers disclosed in EP 961,941 and U.S.Pat. No. 6,221,303; and crosslinkable polyallylamine gluconolactoneprepolymers disclosed in International Application No. WO 2000/31150 andU.S. Pat. No. 6,472,489.

Any suitable UV-absorbing vinylic monomers can be used in apolymerizable composition for preparing a polymer of the invention.Preferred UV absorbing vinylic monomers include without limitation2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole,2-(2-hydroxy-5-acrylyloxyphenyl)-2H-benzotriazole,2-(2-hydroxy-3-methacrylamido methyl-5-tert octylphenyl)benzotriazole,2-(2′-hydroxy-5′-methacrylamidophenyl)-5-chlorobenzotriazole,2-(2′-hydroxy-5′-methacrylamidophenyl)-5-methoxybenzotriazole,2-(2′-hydroxy-5′-methacryloxypropyl-3′-t-butyl-phenyl)-5-chlorobenzotriazole,2-(2′-hydroxy-5′-methacryloxyethylphenyl)benzotriazole,2-(2′-hydroxy-5′-methacryloxypropylphenyl)benzotriazole,2-hydroxy-4-acryloxy alkoxy benzophenone, 2-hydroxy-4-methacryloxyalkoxy benzophenone, allyl-2-hydroxybenzophenone,2-hydroxy-4-methacryloxy benzophenone. In accordance with the invention,the polymerizable composition comprises about 0.2% to about 5.0%,preferably about 0.3% to about 2.5%, more preferably about 0.5% to about1.8%, by weight of a UV-absorbing vinylic monomer.

In a preferred embodiment, a polymer of the invention is asilicone-containing actinically-crosslinkable prepolymer, whichpreferably comprises: (1) monomeric units derived from an amphiphilicsiloxane-containing (meth)acrylamide of any one of formula (1), (2), and(2a) to (2d) as defined above; (2) crosslinking units derived from atleast one polysiloxane-containing crosslinker as described above(preferably a hydrophilized polysiloxane-containing crosslinker asdescribed above) and/or polysiloxane units derived from apolysiloxane-containing vinylic monomer as described above; (3)hydrophilic units derived from at least one hydrophilic vinylic monomeras described above; (4) polymerizable units derived from a chaintransfer agent having a first reactive functional group other than thiolgroup and/or a vinylic monomer having a second reactive functional groupother than ethylenically-unsaturated group, wherein the polymerizableunits each comprise an ethylenically unsaturated group covalentlyattached to one polymerizable unit through the first or second reactivefunctional group; (5) optionally non-silicone crosslinking units derivedfrom at least one non-silicone crosslinker as described above(preferably a non-silicone, hydrophilic crosslinker as described above);and (6) optionally UV-absorbing units derived from a UV-absorbingvinylic monomer as described above. Such a prepolymer is capable ofbeing actinically crosslinked, in the absence of one or more vinylicmonomers, to form a silicone hydrogel contact lens having a watercontent of from about 20% to about 75% (preferably from about 25% toabout 70%, more preferably from about 30% to about 65%) by weight whenfully hydrated, and an oxygen permeability (Dk) of at least about 40barrers (preferably at least about 50 barrers, more preferably at leastabout 60 barrers, and even more preferably at least about 70 barrers).Preferably, such a prepolymer is water soluble or processable. anon-silicone crosslinker as described above

Such a prepolymer is obtained by first polymerizing a polymerizablecomposition including all polymerizable components specified above, toform an intermediary copolymer and then by ethylenically functionalizingthe intermediary copolymer with an ethylenically functionalizing vinylicmonomer having a third reactive functional group capable of reactingwith the first and/or second reactive functional group to form a linkagein a coupling reaction in the presence or absence of a coupling agent toform the prepolymer, wherein the first, second and third reactivefunctional groups independent of one another are selected from the groupconsisting of amino group, hydroxyl group, carboxyl group, acid halidegroup, azlactone group, isocyanate group, epoxy group, aziridine group,and combination thereof. The general procedures for preparingamphiphilic prepolymers are disclosed in U.S. Pat. Nos. 6,039,913,6,043,328, 7,091,283, 7,268,189 and 7,238,750, 7,521,519, 8,071,703,8,044,111, and 8,048,968; in US patent application publication Nos. US2008-0015315 A1, US 2008-0143958 A1, US 2008-0143003 A1, US 2008-0234457A1, US 2008-0231798 A1, 2010/0120939 A1, 2010/0298446 A1, 2012/0088843A1, 2012/0088844 A1, and 2012/0088861 A1; all of which are incorporatedherein by references in their entireties.

In accordance with the invention, the polymerizable units each comprisea basic monomeric unit being a part of a polymer chain of the prepolymerand a pendant or terminal, ethylenically-unsaturated group attachedthereon, wherein each basic monomeric unit is derived from a firstethylenically functionalizing vinylic monomer having a second reactivefunctional group, wherein the pendant or terminal ethylenicallyunsaturated group is derived from a second ethylenically functionalizingvinylic monomer having a third reactive functional group which reactswith one second reactive functional in the presence or absence of acrosslinking agent to form a covalent linkage. The second and thirdreactive functional groups are selected from the group consisting ofamino group, hydroxyl group, carboxyl group, azlactone group, isocyanategroup, epoxy group, aziridine group, acid chloride, and combinationthereof. Examples of such vinylic monomers are those ethylenicallyfunctionalizing vinylic monomers described above. Preferably, the firstethylenically functionalizing vinylic monomer is selected from the groupconsisting of hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate,hydroxyethyl (meth)acrylamide, hydroxypropyl (meth)acrylamide, allylalcohol, aminoethyl (meth)acrylate, aminopropyl (meth)acrylate,aminoethyl (meth)acrylamide, aminopropyl (meth)acrylamide, allyl amine,(meth)acrylic acid, ethylacrylic acid, propylacrylic acid, butylacrylicacid, glycidyl (meth)acrylate, vinyl glycidyl ether, allyl glycidylether, isocynatoethyl (meth)acrylate, 2-(1-aziridinyl) ethyl(meth)acrylate, 3-(1-aziridinyl) propyl (meth)acrylate, 4-(1-aziridinyl)butyl (meth)acrylate, 2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one (VDMO),2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one (IPDMO), and combinationthereof. Most preferably, the first ethylenically functionalizingvinylic monomer is selected from the group consisting of hydroxyethyl(meth)acrylate, hydroxypropyl (meth)acrylate, hydroxyethyl(meth)acrylamide, hydroxypropyl (meth)acrylamide, allyl alcohol,aminoethyl (meth)acrylate, aminopropyl (meth)acrylate, aminoethyl(meth)acrylamide, aminopropyl (meth)acrylamide, allyl amine, andcombinations thereof.

In accordance with the invention, the content of the polymerizable unitsare determined based on weight percentage of the ethylenicallyfunctionalizing vinylic monomer present in the polymerizable compositionfor making an water-processable intermediary copolymer relative to thetotal weight of polymerizable components in the polymerizablecomposition or the weight percentage of the ethylenicallyfunctionalizing vinylic monomer used in ethylenically functionalizingthe intermediary copolymer to form the prepolymer of the invention,relative to the weight of the prepolymer.

A chain transfer agent (containing at least one thiol group) is used tocontrol the molecular weight of the resultant intermediary copolymer.Where a chain transfer has a reactive functional group such as amine,hydroxyl, carboxyl, epoxy, isocyanate, azlactone, or aziridine group, itcan provide terminal or pendant functionality (amine, hydroxyl,carboxyl, epoxy, isocyanate, azlactone, or aziridine group) forsubsequent ethylenical functionalization of the resultant intermediarycopolymer.

In a preferred embodiment, an actinically-crosslinkablesilicone-containing prepolymer of the invention is a water-processableprepolymer that has a high water solubility or dispersibility of atleast about 5%, preferably at least about 10%, more preferably at leastabout 20% by weight in water. The prepolymer is capable of beingactinically crosslinked, in the absence of one or more vinylic monomers,to form a silicone hydrogel contact lens having a water content of fromabout 20% to about 75% (preferably from about 25% to about 70%, morepreferably from about 30% to about 65%) by weight when fully hydrated,an oxygen permeability (Dk) of at least about 40 barrers (preferably atleast about 50 barrers, more preferably at least about 60 barrers, andeven more preferably at least about 70 barrers). A water-processableprepolymer of the invention can find particular use in preparingsilicone hydrogel ophthalmic lenses, in particular contact lenses.

In another aspect, the invention provides a soft contact lens. The softcontact lens of the invention comprises: a silicone hydrogel materialthat is obtained by curing a lens-forming material in a mold, whereinthe lens-forming formulation (or material) comprises at least oneamphiphilic siloxane-containing (meth)acrylamide of the invention (asdescribed above in detail) and/or at least one actinically-crosslinkablesilicone-containing prepolymer of the invention (as described above indetail), wherein the contact lens has a water content of from about 20%to about 75% (preferably from about 25% to about 70%, more preferablyfrom about 30% to about 65%) by weight when fully hydrated, an oxygenpermeability (Dk) of at least about 40 barrers (preferably at leastabout 50 barrers, more preferably at least about 60 barrers, and evenmore preferably at least about 70 barrers), and an elastic modulus offrom about 0.1 MPa to about 2.0 MPa, preferably from about 0.2 MPa toabout 1.5 MPa, more preferably from about 0.3 MPa to about 1.2 MPa, evenmore preferably from about 0.4 MPa to about 1.0 MPa. The lens-formingformulation for obtaining a soft contact lens of the invention canfurther comprise one or more components selected from the groupconsisting of a hydrophilic vinylic monomer, a polysiloxane-containingcrosslinker, a non-silicone crosslinker, a photoinitiator, a thermalinitiator, a UV-absorbing vinylic monomer, a visibility tinting agent(e.g., dyes, pigments, or mixtures thereof), antimicrobial agents (e.g.,preferably silver nanoparticles), a bioactive agent, leachablelubricants, leachable tear-stabilizing agents, and mixtures thereof.

Various embodiments of amphiphili siloxane-containing vinylic monomersof formula (I), polysiloxane-containing crosslinkers, non-siliconecrosslinkers, actinically-crosslinkable silicone containing prepolymersof the inventions, hydrophilic vinylic monomers, UV-absorbing vinylicmonomers, solvents, photoinitiators, and thermal initiators aredescribed above and can be used in this aspect of the invention.

The bioactive agent incorporated in the polymeric matrix is any compoundthat can prevent a malady in the eye or reduce the symptoms of an eyemalady. The bioactive agent can be a drug, an amino acid (e.g., taurine,glycine, etc.), a polypeptide, a protein, a nucleic acid, or anycombination thereof. Examples of drugs useful herein include, but arenot limited to, rebamipide, ketotifen, olaptidine, cromoglycolate,cyclosporine, nedocromil, levocabastine, lodoxamide, ketotifen, or thepharmaceutically acceptable salt or ester thereof. Other examples ofbioactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), alphahydroxyl acids (e.g., glycolic, lactic, malic, tartaric, mandelic andcitric acids and salts thereof, etc.), linoleic and gamma linoleicacids, and vitamins (e.g., B5, A, B6, etc.).

Examples of leachable lubricants include without limitation mucin-likematerials (e.g., polyglycolic acid) and non-crosslinkable hydrophilicpolymers (i.e., without ethylenically unsaturated groups). Anyhydrophilic polymers or copolymers without any ethylenically unsaturatedgroups can be used as leachable lubricants. Preferred examples ofnon-crosslinkable hydrophilic polymers include, but are not limited to,polyvinyl alcohols (PVAs), polyamides, polyimides, polylactone, ahomopolymer of a vinyl lactam, a copolymer of at least one vinyl lactamin the presence or in the absence of one or more hydrophilic vinyliccomonomers, a homopolymer of acrylamide or methacrylamide, a copolymerof acrylamide or methacrylamide with one or more hydrophilic vinylicmonomers, polyethylene oxide (i.e., polyethylene glycol (PEG)), apolyoxyethylene derivative, poly-N—N-dimethylacrylamide, polyacrylicacid, poly 2 ethyl oxazoline, heparin polysaccharides, polysaccharides,and mixtures thereof. The weight-average molecular weight M_(w) of thenon-crosslinkable hydrophilic polymer is preferably from 5,000 to500,000, more preferably from 10,000 to 300,000, even more preferablyfrom 20,000 to 100,000.

Examples of leachable tear-stabilizing agents include, withoutlimitation, phospholipids, monoglycerides, diglycerides, triglycerides,glycolipids, glyceroglycolipids, sphingolipids, sphingo-glycolipids,fatty alcohols, fatty acids, mineral oils, and mixtures thereof.Preferably, a tear stabilizing agent is a phospholipid, a monoglyceride,a diglyceride, a triglyceride, a glycolipid, a glyceroglycolipid, asphingolipid, a sphingo-glycolipid, a fatty acid having 8 to 36 carbonatoms, a fatty alcohol having 8 to 36 carbon atoms, or a mixturethereof.

In accordance with the invention, a lens-forming formulation (ormaterial) is a fluid composition, which can be a solution or a melt at atemperature from about 20° C. to about 85° C. A lens forming formulationcan be prepared by dissolving all of the desirable components in anysuitable solvent known to a person skilled in the art, e.g., any onesolvent described above. Preferably, a lens-forming material is asolution of all the desirable components in water, 1,2-propylene glycol,a polyethyleneglycol having a molecular weight of about 400 Daltons orless, or a mixture thereof.

Lens molds for making contact lenses are well known to a person skilledin the art and, for example, are employed in cast molding or spincasting. For example, a mold (for cast molding) generally comprises atleast two mold sections (or portions) or mold halves, i.e. first andsecond mold halves. The first mold half defines a first molding (oroptical) surface and the second mold half defines a second molding (oroptical) surface. The first and second mold halves are configured toreceive each other such that a lens forming cavity is formed between thefirst molding surface and the second molding surface. The moldingsurface of a mold half is the cavity-forming surface of the mold and indirect contact with lens-forming material.

Methods of manufacturing mold sections for cast-molding a contact lensare generally well known to those of ordinary skill in the art. Theprocess of the present invention is not limited to any particular methodof forming a mold. In fact, any method of forming a mold can be used inthe present invention. The first and second mold halves can be formedthrough various techniques, such as injection molding or lathing.Examples of suitable processes for forming the mold halves are disclosedin U.S. Pat. No. 4,444,711 to Schad; U.S. Pat. No. 4,460,534 to Boehm etat; U.S. Pat. No. 5,843,346 to Morrill; and U.S. Pat. No. 5,894,002 toBoneberger et al., which are also incorporated herein by reference.

Virtually all materials known in the art for making molds can be used tomake molds for making contact lenses. For example, polymeric materials,such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade8007-S10 (clear amorphous copolymer of ethylene and norbornene, fromTicona GmbH of Frankfurt, Germany and Summit, N.J.), or the like can beused. Other materials that allow UV light transmission could be used,such as quartz glass and sapphire.

In accordance with the invention, the lens-forming formulation (orcomposition) can be introduced (dispensed) into a cavity formed by amold according to any known methods.

After the lens-forming composition is dispensed into the mold, it ispolymerized to produce a contact lens. Crosslinking may be initiatedthermally or actinically, preferably by exposing the lens-formingcomposition in the mold to a spatial limitation of actinic radiation tocrosslink the polymerizable components in the lens-forming composition.

Where the lens-forming composition comprises a UV-absorbing vinylicmonomer, a benzoylphosphine oxide photoinitiator is preferably used asthe photoinitiator in the invention. Preferred benzoylphosphine oxidephotoinitiators include without limitation2,4,6-trimethylbenzoyldiphenylophosphine oxide;bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide; andbis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. It isunderstood that any photoinitiators other than benzoylphosphine oxideinitiators can be used in the invention.

Opening of the mold so that the molded article can be removed from themold may take place in a manner known per se.

The molded contact lens can be subject to lens extraction to removeunpolymerized polymerizable components. The extraction solvent can beany solvent known to a person skilled in the art. Examples of suitableextraction solvent are those described above. Preferably, water or anaqueous solution is used as extraction solvent. After extraction, lensescan be hydrated in water or an aqueous solution of a wetting agent(e.g., a hydrophilic polymer).

The molded contact lenses can further subject to further processes, suchas, for example, surface treatment, packaging in lens packages with apackaging solution which can contain about 0.005% to about 5% by weightof a wetting agent (e.g., a hydrophilic polymer described above or thelike known to a person skilled in the art) and/or a viscosity-enhancingagent (e.g., methyl cellulose (MC), ethyl cellulose,hydroxymethylcellulose, hydroxyethyl cellulose (HEC),hydroxypropylcellulose (HPC), hydroxypropylmethyl cellulose (HPMC), or amixture thereof); sterilization such as autoclave at from 118 to 124° C.for at least about 30 minutes; and the like.

In a further aspect, the invention provides a method for making siliconehydrogel contact lenses. The method comprises the steps of: introducinga lens formulation into a mold for making contact lenses, wherein thelens-forming formulation comprises (a) a solvent selected from the groupconsisting of water, 1,2-propylene glycol, a polyethyleneglycol having amolecular weight of about 400 Daltons or less, and mixtures thereof, (b)at least one amphiphilic siloxane-containing (meth)acrylamide of formula(1) or (2) (as described above in detail) and/or at least oneactinically-crosslinkable silicone containing prepolymer of theinvention as described above in detail, and (c) at least one componentselected from the group consisting of a hydrophilic vinylic monomer (asdescribed above in detail), a hydrophilized polysiloxane-containingcrosslinker (as described above in detail), a hydrophilic crosslinker(as described above in detail), a photoinitiator (as described above indetail), a thermal initiator (as described above in detail), aUV-absorbing vinylic monomer (as described above in detail), avisibility tinting agent (e.g., dyes, pigments, or mixtures thereof),antimicrobial agents (e.g., preferably silver nanoparticles), abioactive agent (as described above in detail), leachable lubricants (asdescribed above in detail), leachable tear-stabilizing agents (asdescribed above in detail), and mixtures thereof; polymerizing the lensformulation in the mold to form a silicone hydrogel contact lens,wherein the formed silicone hydrogel contact lens has a water content offrom about 20% to about 75% (preferably from about 25% to about 70%,more preferably from about 30% to about 65%) by weight when fullyhydrated, an oxygen permeability (Dk) of at least about 40 barrers(preferably at least about 50 barrers, more preferably at least about 60barrers, and even more preferably at least about 70 barrers), and anelastic modulus of from about 0.1 MPa to about 2.0 MPa, preferably fromabout 0.2 MPa to about 1.5 MPa, more preferably from about 0.3 MPa toabout 1.2 MPa, even more preferably from about 0.4 MPa to about 1.0 MPa.

Various embodiments of amphiphilic siloxane-containing vinylic monomersof formula (1) or (2), actinically-crosslinkable silicone containingprepolymers of the invention, lens forming formulations, hydrophilicvinylic monomers, hydrophilized polysiloxane-containing crosslinkers,hydrophilic crosslinkers, solvents, UV-absorbing vinylic monomers,photoinitiators, thermal initiators, visibility tinting agents,antimicrobial agents, bioactive agents, leachable lubricants, leachabletear-stabilizing agents, molds, polymerizing techniques, and postmolding processes are described above and can be used in this aspect ofthe invention.

In a preferred embodiment, the resultant silicone hydrogel contact lensis extracted with water or an aqueous solution.

In another preferred embodiment, the mold is a reusable mold and thelens-forming composition is cured (i.e., polymerized) actinically undera spatial limitation of actinic radiation to form a silicone hydrogelcontact lens. Examples of preferred reusable molds are those disclosedin U.S. Pat. Nos. 6,627,124, 6,800,225, 7,384,590, and 7,387,759, whichare incorporated by reference in their entireties. Reusable molds can bemade of quartz, glass, sapphire, CaF₂, a cyclic olefin copolymer (suchas for example, Topas® COC grade 8007-S10 (clear amorphous copolymer ofethylene and norbornene) from Ticona GmbH of Frankfurt, Germany andSummit, N.J., Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville,Ky.), polymethylmethacrylate (PMMA), polyoxymethylene from DuPont(Delrin), Ultem® (polyetherimide) from G.E. Plastics, PrimoSpire®, andcombinations thereof.

Although various embodiments of the invention have been described usingspecific terms, devices, and methods, such description is forillustrative purposes only. The words used are words of descriptionrather than of limitation. It is to be understood that changes andvariations may be made by those skilled in the art without departingfrom the spirit or scope of the present invention, which is set forth inthe following claims. In addition, it should be understood that aspectsof the various embodiments may be interchanged either in whole or inpart or can be combined in any manner and/or used together. Therefore,the spirit and scope of the appended claims should not be limited to thedescription of the preferred versions contained therein.

The previous disclosure will enable one having ordinary skill in the artto practice the invention. In order to better enable the reader tounderstand specific embodiments and the advantages thereof, reference tothe following non-limiting examples is suggested. However, the followingexamples should not be read to limit the scope of the invention.

Example 1

The apparent oxygen permeability of a lens and oxygen transmissibilityof a lens material is determined according to a technique similar to theone described in U.S. Pat. No. 5,760,100 and in an article by Wintertonet al., (The Cornea: Transactions of the World Congress on the Cornea111, H.D. Cavanagh Ed., Raven Press: New York 1988, pp 273-280), both ofwhich are herein incorporated by reference in their entireties. Oxygenfluxes (J) are measured at 34° C. in a wet cell (i.e., gas streams aremaintained at about 100% relative humidity) using a Dk1000 instrument(available from Applied Design and Development Co., Norcross, Ga.), orsimilar analytical instrument. An air stream, having a known percentageof oxygen (e.g., 21%), is passed across one side of the lens at a rateof about 10 to 20 cm³/min., while a nitrogen stream is passed on theopposite side of the lens at a rate of about 10 to 20 cm³/min. A sampleis equilibrated in a test media (i.e., saline or distilled water) at theprescribed test temperature for at least 30 minutes prior to measurementbut not more than 45 minutes. Any test media used as the overlayer isequilibrated at the prescribed test temperature for at least 30 minutesprior to measurement but not more than 45 minutes. The stir motor'sspeed is set to 1200±50 rpm, corresponding to an indicated setting of400±15 on the stepper motor controller. The barometric pressuresurrounding the system, P_(measured), is measured. The thickness (t) ofthe lens in the area being exposed for testing is determined bymeasuring about 10 locations with a Mitotoya micrometer VL-50, orsimilar instrument, and averaging the measurements. The oxygenconcentration in the nitrogen stream (i.e., oxygen which diffusesthrough the lens) is measured using the DK1000 instrument. The apparentoxygen permeability of the lens material, Dk_(app), is determined fromthe following formula:

Dk _(app) =Jt/(P _(oxygen))

where J=oxygen flux [microliters O₂/cm²-minute]

P_(oxygen)=(P_(measured)−P_(water) vapor)=(% O₂ in air stream) [mmHg]=partial pressure of oxygen in the air stream

P_(measured)=barometric pressure (mm Hg)

P_(water) vapor=0 mm Hg at 34° C. (in a dry cell) (mm Hg)

P_(water) vapor=40 mm Hg at 34° C. (in a wet cell) (mm Hg)

t=average thickness of the lens over the exposed test area (mm)

Dk_(app) is expressed in units of barrers.

The apparent oxygen transmissibility (Dk/t) of the material may becalculated by dividing the apparent oxygen permeability (Dk_(app)) bythe average thickness (t) of the lens.

The above described measurements are not corrected for the so-calledboundary layer effect which is attributable to the use of a water orsaline bath on top of the contact lens during the oxygen fluxmeasurement. The boundary layer effect causes the reported value for theapparent Dk of a silicone hydrogel material to be lower than the actualintrinsic Dk value. Further, the relative impact of the boundary layereffect is greater for thinner lenses than with thicker lenses. The neteffect is that the reported Dk appear to change as a function of lensthickness when it should remain constant.

The intrinsic Dk value of a lens can be estimated based on a Dk valuecorrected for the surface resistance to oxygen flux caused by theboundary layer effect as follows.

Measure the apparent oxygen permeability values (single point) of thereference lotrafilcon A (Focus® N&D® from CIBA VISION CORPORATION) orlotrafilcon B (AirOptix™ from CIBA VISION CORPORATION) lenses using thesame equipment. The reference lenses are of similar optical power as thetest lenses and are measured concurrently with the test lenses.

Measure the oxygen flux through a thickness series of lotrafilcon A orlotrafilcon B (reference) lenses using the same equipment according tothe procedure for apparent Dk measurements described above, to obtainthe intrinsic Dk value (Dk_(i)) of the reference lens. A thicknessseries should cover a thickness range of approximately 100 μm or more.Preferably, the range of reference lens thicknesses will bracket thetest lens thicknesses. The Dk_(app) of these reference lenses must bemeasured on the same equipment as the test lenses and should ideally bemeasured contemporaneously with the test lenses. The equipment setup andmeasurement parameters should be held constant throughout theexperiment. The individual samples may be measured multiple times ifdesired.

Determine the residual oxygen resistance value, R_(r), from thereference lens results using equation 1 in the calculations.

$\begin{matrix}{R_{r} = \frac{\sum\limits^{\;}\left( {\frac{t}{{Dk}_{app}} - \frac{t}{{DK}_{i}}} \right)}{n}} & (1)\end{matrix}$

in which t is the thickness of the test lens (i.e., the reference lenstoo), and n is the number of the reference lenses measured. Plot theresidual oxygen resistance value, R_(r) vs. t data and fit a curve ofthe form Y=a+bX where, for the jth lens, Y_(j)=(ΔP/J)_(j) and X=t_(j).The residual oxygen resistance, R_(r) is equal to a.

Use the residual oxygen resistance value determined above to calculatethe correct oxygen permeability Dk_(c) (estimated intrinsic Dk) for thetest lenses based on Equation 2.

Dk _(c) =t/[(t/Dk _(a))−R _(r)]  (2)

The estimated intrinsic Dk of the test lens can be used to calculatewhat the apparent Dk (Dk_(a) _(—) _(std)) would have been for a standardthickness lens in the same test environment based on Equation 3. Thestandard thickness (t_(std)) for lotrafilcon A=85 μm. The standardthickness for lotrafilcon B=60 μm.

Dk _(a) _(—) _(std) =t _(std)/[(t _(std) /Dk _(c))+R _(r) _(—)_(std)]  (3)

Ion Permeability Measurements.

The ion permeability of a lens is measured according to proceduresdescribed in U.S. Pat. No. 5,760,100 (herein incorporated by referencein its entirety. The values of ion permeability reported in thefollowing examples are relative ionoflux diffusion coefficients(D/D_(ref)) in reference to a lens material, Alsacon, as referencematerial. Alsacon has an ionoflux diffusion coefficient of 0.314×10⁻³mm²/minute.

Folding Mark Determination.

A Contact Lens Optical Quality Analyzer (CLOQA) is developed todetermine optical distortions caused by surface deformations and otherdefects in the contact lens, based on the principle of the Foucaultknife-edge test. A person skilled in the art understands how to select,align and arrange various optics elements to create collimating light,to illuminate a contact lens, and to capture an image with a device (forexample, such as, a CCD camera). The test involves illuminating thecontact lens with a near-collimated light, placing a Foucault knife edgenear the focal point, moving the knife-edge to block off most of thefocused light, and capturing the image of contact lens with a device,for example CCD camera behind the Foucault knife edge. Where there is nooptical distortion in the contact lens, all light rays passing throughthe contact lens come to focus at the knife edge and most of thewell-focused light will be blocked off. For areas outside the opticalzone which has no focusing function, the knife-edge will block the lightfrom half of the lens to make it dark, while the other half appearbright. If the contact lens has no optical distortions in its opticalzone, the whole optical zone will be uniformly dark or bright dependingon how much light is blocked by the knife-edge. Where there are opticaldistortions on the contact lens, light passing through such areas ingeneral does not fall into the main focus and may be either blocked bythe knife edge (appearing dark) or pass through freely (appearingbright). The level of contrast not only depends on the amplitude of thedistortion, but also depends on the fine position of the knife-edge. Thedefective areas appear as contrast features in the CLOQA image. Theknife-edge test with CLOQA is designed as a qualitative testing devicefor optical distortions in the optical zone.

Folding mark study is carried out as follows. Three autoclaved and/ornot autoclaved contact lenses are used in the study. First, images ofthe contact lenses are taken with the CLOQA. Second, each lens is foldedwith fingers twice (creating two perpendicular fold lines) and then itsimage is taken immediately with the CLOQA. Third, the image of eachcontact lens about 15 minutes after folding is taken with the CLOQA.Three types of CLOQA images are obtained: original one (i.e., withoutfolding), immediately after folding, and about 15 minutes after folding.The folding mark study allows to determine the appearance of the foldingline changing over time.

1-14. (canceled)
 15. A method for making silicone hydrogel contactlenses, comprising the steps of: introducing a lens-forming formulationinto a mold for making contact lenses, wherein the lens-formingformulation comprises (a) a solvent selected from the group consistingof water, 1,2-propylene glycol, a polyethyleneglycol having a molecularweight of about 400 Daltons or less, and mixtures thereof, (b) at leastone amphiphilic siloxane-containing (meth)acrylamide of formula (1) or(2)

in which A₁, A₂, A₃ and A₄ independent of one another are a C₁-C₆ alkyl,phenyl or benzyl, r1 is an integer of 2 or 3, R′ is H or C₁-C₄ alkyl,R₁₀ is hydrogen or methyl, R₁₁ is a linear or branched C₂-C₆ alkylenedivalent radical which may be substituted with one or more hydroxylgroups, R₁₂ is C₁-C₄ alkoxy, Z₁ and Z₂ independent of each other are adirect bond or a linear or branched C₁-C₄ alkylene divalent radical, Z₃is C₂-C₄ alkylene divalent radical, Z₄, Z₅, and Z₆ independent of oneanother are a direct bond or a linear or branched C₁-C₂₀ alkylenedivalent radical which may have one or more ether, thio, amine,carbonyl, or amido linkages in their main chain, X₁ is —O—CO—NH— or—O—CO—NH—R₁₃—NH—CO—O— in which R₁₃ is a linear or branched C₂-C₁₂alkylene divalent radical or a C₅-C₄₅ cycloaliphatic oraliphatic-cycloaliphatic divalent radical, X₂ and X₃ independent of eachother are selected from the group consisting of direct bond, —O—, —NR′—,—CO—NR′—, —NR′—CO—, —O—CO—NH—, —NH—CO—O—, —NR′—CO—NH—, —NH—CO—NR′—,—S—CO—NH—, —NH—CO—S—, —S—, —CO—O—, —O—CO—, —O—CO—NH—R₁₃—NH—CO—O—, and—NH—CO—NH—R₁₃—NH—CO—NH—, in which R′ and R₁₃ are as defined above, q1 isan integer from 2 to 50, q2 is an integer from 3 to 20, (c) at least onehydrophilic vinylic monomer, and (d) at least one component selectedfrom the group consisting of a hydrophilized polysiloxane-containingcrosslinker, a hydrophilic crosslinker, a photoinitiator, a thermalinitiator, a UV-absorbing vinylic monomer, a visibility tinting agent,an antimicrobial agent, a bioactive agent, a leachable lubricant, aleachable tear-stabilizing agent, and mixtures thereof; polymerizing thelens-forming formulation in the mold to form a silicone hydrogel contactlens, wherein the formed silicone hydrogel contact lens has a watercontent of from about 20% to about 75% by weight when fully hydrated, anoxygen permeability (Dk) of at least about 40 barrers, and an elasticmodulus of from about 0.1 MPa to about 2.0 MPa.
 16. The method of claim15, further comprising the step of extracting the molded siliconehydrogel contact lens with water or an aqueous solution.
 17. The methodof claim 16, wherein the mold is a reusable mold and the lens-formingcomposition is cured actinically under a spatial limitation of actinicradiation to form the silicone hydrogel contact lens.
 18. A method formaking silicone hydrogel contact lenses, comprising the steps of:introducing a lens-forming formulation into a mold for making contactlenses, wherein the lens-forming formulation comprises (a) a solventselected from the group consisting of water, 1,2-propylene glycol, apolyethyleneglycol having a molecular weight of about 400 Daltons orless, and mixtures thereof, (b) at least one actinically-crosslinkedsilicone containing prepolymer which is obtained by polymerixing apolymerizable composition comprising (i)

in which A₁, A₂, A₃ and A₄ independent of one another are a C₁-C₆ alkyl,phenyl or benzyl, r1 is an integer of 2 or 3, R′ is H or C₁-C₄ alkyl,R₁₀ is hydrogen or methyl, R₁₁ is a linear or branched C₂-C₆ alkylenedivalent radical which may be substituted with one or more hydroxylgroups, R₁₂ is C₁-C₄ alkoxy, Z₁ and Z₂ independent of each other are adirect bond or a linear or branched C₁-C₄ alkylene divalent radical, Z₃is C₂-C₄ alkylene divalent radical, Z₄, Z₅, and Z₆ independent of oneanother are a direct bond or a linear or branched C₁-C₂₀ alkylenedivalent radical which may have one or more ether, thio, amine,carbonyl, or amido linkages in their main chain, X₁ is —O—CO—NH— or—O—CO—NH—R₁₃—NH—CO—O— in which R₁₃ is a linear or branched C₂-C₁₂alkylene divalent radical or a C₅-C₄₅ cycloaliphatic oraliphatic-cycloaliphatic divalent radical, X₂ and X₃ independent of eachother are selected from the group consisting of direct bond, —O—, —NR′—,—CO—NR′—, —NR′—CO—, —O—CO—NH—, —NH—CO—O—, —NR′—CO—NH—, —NH—CO—NR′—,—S—CO—NH—, —NH—CO—S—, —S—, —CO—O—, —O—CO—, —O—CO—NH—R₁₃—NH—CO—O—, and—NH—CO—NH—R₁₃—NH—CO—NH—, in which R′ and R₁₃ are as defined above, q1 isan integer from 2 to 50, q2 is an integer from 3 to 20, (ii) at leastone polysiloxane-containing crosslinker and/or at least one non-siliconecrosslinker, (iii) at least one hydrophilic vinylic monomer, and (iv)ethylenically-unsaturated groups, and (c) at least one componentselected from the group consisting of a hydrophilic vinylic monomer, ahydrophilized polysiloxane-containing crosslinker, a hydrophiliccrosslinker, a photoinitiator, a thermal initiator, a UV-absorbingvinylic monomer, a visibility tinting agent, an antimicrobial agent, abioactive agent, a leachable lubricant, a leachable tear-stabilizingagent, and mixtures thereof; polymerizing the lens-forming formulationin the mold to form a silicone hydrogel contact lens, wherein the formedsilicone hydrogel contact lens has a water content of from about 20% toabout 75% by weight when fully hydrated, an oxygen permeability (Dk) ofat least about 40 barrers, and an elastic modulus of from about 0.1 MPato about 2.0 MPa.
 19. The method of claim 18, further comprising thestep of extracting the molded silicone hydrogel contact lens with wateror an aqueous solution.
 20. The method of claim 19, wherein the mold isa reusable mold and the lens-forming composition is cured actinicallyunder a spatial limitation of actinic radiation to form the siliconehydrogel contact lens.